PROJECT SUMMARY/ABSTRACT The University of California Preclinical Animal Study Site (UC PASS) is a collaborative effort between UC Davis and UC San Diego that brings together the scientific expertise, state of the art technologies and facilities, and institutional support to achieve the primary objectives goals of the PASS, which are to: 1) develop animal models that best complement the endurance and resistance training protocols used in the human trials, and 2) provide organ and tissue samples collected at multiple time points after both acute and chronic exercise for analysis by the Chemical Analysis Sites. The animal studies to be undertaken by the PASS will begin to elucidate the molecular pathways responsible for the acute and chronic effects of both endurance and resistance exercise on individual organs, as well as identify the interactions between organs; the goal being to understand the mechanisms by which different modes of physical activity impart their health benefits. In order to reach this goal, experts in model development and phenotyping of the resulting muscle and global health adaptations will be essential. The UC PASS team has exactly these traits. The team acknowledges that the ultimate animal model and exercise tests to be utilized in the PASS will be determined by the Molecular Transducers of Physical Activity Common (MoTrPAC) Steering Committee. In this application we provide a strong rationale and justification for the use of the rat as the animal model and propose specific endurance and resistance exercise programs to be used in Phase I of the PASS, highlighting the major advantages and limitations of each paradigm. In Phase II of the PASS we build on the models established in Phase I and propose three specific aims to begin to produce a standard curve of molecular transducers versus adaptive response to exercise. In Phase II we propose to exercise animals of increasing age or increasing adiposity, determine the adaptive response to 12 weeks of training, and relate this with the acute molecular transducer response to exercise. With this secondary screen, we will be able to identify molecular transducers that directly correlate with the local or global health benefits of exercise. We will then use this information to test the genetic requirement for these molecular transducers for the health benefits of exercise. The UC PASS is composed of an exceptional team of primary investigators and key collaborators/advisors with expertise in the development of animal models of exercise, the molecular response to exercise, and applied human exercise interventions. This team will provide leadership and the necessary skill sets to successfully model human exercise in animals, which is essential to the success of the MoTrPAC Common Fund and achievement of its goal: to define and understand the cellular and molecular mechanisms of the human health benefits of physical activity.